ω-3脂肪酸对胰腺癌细胞的抗肿瘤作用及其分子机制

Antitumor effect of ω-3 fatty acid on pancreatic cancer cells SW1990 in vitro and its molecular mechanism

背景与目的:流行病学调查表明:饮食中高ω-3脂肪酸摄入的人群恶性肿瘤的发病率明显降低,但其抗肿瘤的具体机制尚不明确,且目前对其是否具有抗胰腺癌作用及其机制研究甚少。本研究探讨ω-3脂肪酸对胰腺癌细胞株增殖、凋亡及细胞周期调控蛋白cyclinEmRNA转录的影响。方法:采用EPA、DHA作用于胰腺癌细胞株SW19900～48h,MTT法检测对细胞生长抑制的影响,采用实时定量PCR分析40μg/mlDHA和EPA作用于0～48h后细胞周期蛋白cyclinEmRNA表达变化,流式细胞技术观察DHA和EPA处理后细胞凋亡率的变化。结果:EPA、DHA能以时间和剂量依赖方式抑制SW1990细胞的生长(P<0.01,见表1);EPA、DHA还能显著抑制cyc-linEmRNA的表达,其效应具有时间依赖性(P<0.05,见图1C);不同浓度的EPA和DHA能以剂量依赖性方式诱导SW1990细胞发生凋亡(P<0.01)。结论:ω-3脂肪酸可以抑制胰腺癌细胞株SW1990的增殖并促进其凋亡,ω-3脂肪酸对cyclinE表达的抑制可能是其抗肿瘤的分子机制之一。

Background and purpose：The major composition of ω-3 fatty acid are ecosapeatanolic acid（EPA）or ducosahexenoic acid（DHA）.Epidemiological studies indicated that the risk of malignancy was decreased significantly in the population with high ω-3 fatty acid intake,however the mechanisms of its antitumor effect were not well elucidated.Additionally,there was limited evidence in its effect on pancreatic cancer.This study was therefore done to investigate the effects of ω-3 fatty acid on pancreatic cancer cells proliferation,apoptosis and the mRNA expression of cell cycle regulatory protein cyclin E.Methods：SW1990 cell lines were cultured with either EPA or DHA and the proliferation of SW1990 cells was determined by MTT assay.Treated by EPA or DHA at different times,the cyclin E mRNA expression of SW1990 was detected by real-time PCR.24 hr after being cultured with EPA or DHA at the concentration of 20,40 and 60 μg/ml,the apoptosis rate of SW1990 cells was analyzed by flow cytometry（FCM）.Results：EPA and DHA could inhibit the proliferation of SW1990 cells significantly in a dose and time-dependent way（P〈0.01）.Meanwhile,the cyclin E mRNA expression of SW1990 was markedly inhibited by the addition of 40 μg/ml EPA or DHA for 12,24,36,48 hours,and the inhibition was time-dependent（P〈0.05）.Moreover,24 hr after being cultured with EPA or DHA at varying concentrations,the apoptosis rate of SW1990 cells was in a dose-dependent manner（P〈0.01）.Conclusions：ω-3 fatty acid could inhibit the proliferation of pancreatic cancer cells and induce apoptosis.The down regulating of cyclin E expression might be one of the molecular mechanisms for its antitumor effect on pancreatic cancer.